Clinical Effectiveness of the Fixed‐Dose vs Free‐Dose Triple Combinations in Patients with Uncontrolled Arterial Hypertension

D. Yu. Shukurova, G. A. Khamidullaeva, G. Zh. Abdullaeva, Kh. F. Yusupova, A. D. Yuldasheva, Sh. Fayzullaeva, Zh. B. Safarov, Sh. M. Masharipov

For citation: Shukurova DYu, Khamidullaeva GA, Abdullaeva GZh, Yusupova KhF, Yuldasheva AD, Fayzullaeva Sh, Safarov ZhB, Masharipov ShM. Clinical Effectiveness of the Fixed‐Dose vs Free‐Dose Triple Combinations in Patients with Uncontrolled Arterial Hypertension. International Journal of Biomedicine. 2024;14(2):253-259. doi:10.21103/Article14(2)_OA2
Originally published June 5, 2024


Background: The purpose of our study was a comparative assessment of the antihypertensive effectiveness of 2 triple combination antihypertensive therapy (AHT) regimens in a free-dose and fixed-dose combination of perindopril, indapamide, and amlodipine in hypertensive patients with high cardiovascular risk and a poor response to the 2-drug combinations in the clinic practice.
Methods and Results: Our study included 143 patients (79 men and 88 women) with arterial hypertension (AH) Grades 1-3 (ESC/ESH, 2018) and high cardiovascular risk who did not achieve the target blood pressure (TBP) on dual combination AHT. The mean age of patients was 55.76±9.35 years; the average duration of AH was 10.69±6.61 years. All patients underwent the examinations according to the 2018 ESC/ESH Guidelines for the management of arterial hypertension.
Patients included in the study were divided into 2 groups using the envelope method: Group 1 (n=84) received a fixed-dose, triple combination of perindopril, indapamide, and amlodipine; Group 2 (n=83) received a free-dose combination of these drugs. In both groups, treatment began after discontinuation of previous therapy, with a low dose of a triple combination of antihypertensive drugs (perindopril [5 mg/day], indapamide [1.25 mg/day], amlodipine [5 mg/day]) in the form of a fixed or free combination. The initial doses of perindopril/indapamide/amlodipine in both groups were not statistically different: 6.9±2.4/1.74±0.6/7.1±2.4mg/day in Group 1 and 6.9±2.7/1.95±0.6/7.1±2.5 mg/day in Group 2. After 4 weeks of therapy, if necessary, the doses of drugs were increased, starting with perindopril; the next adjustment of drug doses was carried out after 12 weeks of therapy. The final treatment results were determined after 24 weeks of AHT.
Target blood pressure (TBP) of <140/90 mmHg was reached by 94.4% of patients in Group 1 and 83.3% in Group 2 (χ²=7.471, Р=0,006); TBP of <130/80 mmHg was reached by 70% of patients in Group 1 and 42% in Group 2 (χ²=11.61, Р=0,0001).  A significant improvement in the diurnal BP profile was also revealed during treatment. According to ABPM data, both groups achieved TBP in terms of the average 24-h and average daytime systolic blood pressure (SBP) and diastolic blood pressure (DBP). Regarding average nighttime SBP and DBP and normalization of average nighttime diastolic blood pressure variability, target values were achieved only in Group 1(P=0.028).
In both groups, 24-week triple-combination therapy led to a significant decrease in central SBP, central DBP, and pulse wave velocity (PWV). At the same time, the positive dynamics of central SBP were more pronounced in Group 1 than in Group 2 (Table 4), and PWV in Group 1 reached standard values.
Conclusion: The results of our study showed that in the treatment of uncontrolled hypertension on previous therapy in AH patients with high cardiovascular risk, a single-pill triple combination of the ACEI perindopril, the CCB amlodipine, and the thiazide-like diuretic indapamide contributed to the effective daily blood pressure control, the improvement of diurnal blood pressure profile, and a positive effect on central blood pressure and PWV, thereby having a positive impact on the prognosis and quality of life of AH patients with high cardiovascular risk.

arterial hypertension • antihypertensive therapy • target blood pressure • single-pill triple combination
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Received February 3, 2024.
Accepted March 14, 2024.
©2024 International Medical Research and Development Corporation.